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GG-13 ‘EpiTOF’ – a new method for characterizing the epigenetic landscape in SLE
  1. Paul J Utz
  1. Department of Medicine, Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA


Background SLE is a complex disease with very few approved therapeutic options. Unique opportunities exist to characterize blood cells, tissues such as kidney and skin, urine, serum and plasma as part of ongoing longitudinal cohort studies such as Accelerating Medicines Partnership (AMP) and Autoimmunity Centers of Excellence (ACE), and investigator initiated or company-sponsored clinical trials. The epigenome, in particular, is an area of great interest.

Materials and methods We have recently published a new method called Epigenetic Time of Flight (EpiTOF), a mass cytometry based method that enables broad characterization of posttranslational modifications (PTMs) of histones in health and disease. Our initial studies demonstrated marked heterogeneity in younger vs older healthy adults. Twin studies showed that ∼70% of variation is related to environment. Twenty-two different populations of blood cells were profiled, and the PTMs alone were sufficient to identify cell populations, even in the absence of cell surface markers.

Results Blood derived from multiple diseases was provided through the ACE Collaborative Network and local Stanford investigators and subjected to EpiTOF analysis followed by complex computational analysis. I will present ongoing studies in SLE, SSc, RA, IBD, JIA, vaccines, and infectious diseases using EpiTOF.

Conclusions EpiTOF and other multiplexed assays (such as autoantibody profiling) of samples derived from SLE patients, as well as patients with related autoimmune diseases, have tremendous potential and should be included in all clinical trials, with a goal to better understand pathogenesis and to identify novel therapeutic targets.

Acknowledgements NIAID/DAIT, Henry Gustav Floren Trust, Baxter Foundation, and many patients with SLE who have provided samples.

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